This is a supplemental proposal to provide salary support for Dr. Andrew H. J. Wang so he can combine forces with our research group, and pursue the x-ray structure analyses of crystalline DNA and of its complexes with drugs and control proteins. The specific aims of our research are to use x-ray crystallography to study (1) the structure of DNA molecules of carefully chosen sequences, and (2) the complexes of DNA with drugs of antitumor, antiviral and antibiotic effectiveness, and with lac repressor or the repressor headpiece. We want to discover the extent to which specific base sequence affects the overall helix geometry, and whether this is one element in the recognition of DNA sequences by control proteins. We also want to find out how different classes of drugs bind to DNA, and how this contributes to their pharmaceutical behavior. Immediate goals are to complete the refinement of the DNA dodecamer CGCGAATTCGCG and its complex with Cisplatin, or cis-dichlorodiaminoplatinum(II), Distamycin A and Netropsin, to solve the structure of CCCAAATTTGGG and investigate its binding to other intercalating and nonintercalating drugs, and to begin the crystal structure analysis of the lac operator, hopefully also with its Actinomycin complex.